In these next phases, the continuing studies will be on the spironolactone effects on cytochrome P-450, in vitro, on human tissues, namely testes and adrenals. In addition, the main thrust is directed at the study of the general mechanism by which spironolactone affects endocrine tissues. In addition to the study of the in vitro effects of spironolactone on human testicular and adrenal microsomal cytochrome P-450, and the study of the possible transfer of the sulfur moiety to cytochrome P-450 with the use of 35S labeled spironolactone, the experimentation will largely involve molecular orbital and quantum mechanical approaches to what is occurring at the molecular level using spectral and ESR analyses. Closely related series of aromatic and halogenated hydrocarbons will be used as model system in interacting with the porphyrin moiety of the cytochrome P-450. We will attempt the calculation of the changes of the complexes in terms of transition energies, oscillatory strengths, and spin densities.